A Macrocyclic Hybrid PET/MRI Probe for Quantitative Perfusion Imaging In Vivo.

Perfusion dynamics play a vital role in delivering essential nutrients and oxygen to tissues while removing metabolic waste products. Imaging techniques such as magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET) use contrast agents to visualize perfusion and clearance patterns; however, each technique has specific limitations. Hybrid PET/MRI combines the quantitative power and sensitivity of PET with the high functional and anatomical detail of MRI and holds great promise for precision in molecular imaging. However, the development of dual PET/MRI probes has been hampered by challenging synthesis and radiolabeling. Here, we present a novel PET/MRI probe, [18F][Gd(FL1)], which exhibits excellent stability comparable to macrocyclic MRI contrast agents used in clinical practice. The unique molecular design of [18F][Gd(FL1)] allows selective and expeditious radiolabeling of the gadolinium chelate in the final synthetic step. Leveraging the strengths of MRI and PET signals, the probe enables quantitative in vivo mapping of perfusion and excretion dynamics through an innovative voxel-based analysis. The diagnostic capabilities of [18F][Gd(FL1)] were demonstrated in a pilot study on healthy mice, successfully detecting early cases of unilateral renal dysfunction. This study introduces a new approach for PET/MRI and emphasizes a streamlined probe design for improved diagnostic accuracy.

Pick up and dispose of pollutants from water via temperature-responsive micellar copolymers on magnetite nanorobots.

Nano/micromotor technology is evolving as an effective method for water treatment applications in comparison to existing static mechanisms. The dynamic nature of the nano/micromotor particles enable faster mass transport and a uniform mixing ensuring an improved pollutant degradation and removal. Here we develop thermosensitive magnetic nanorobots (TM nanorobots) consisting of a pluronic tri-block copolymer (PTBC) that functions as hands for pollutant removal. These TM nanorobots are incorporated with iron oxide (Fe3O4) nanoparticles as an active material to enable magnetic propulsion. The pickup and disposal of toxic pollutants are monitored by intermicellar agglomeration and separation of PTBC at different temperatures. The as-prepared TM nanorobots show excellent arsenic and atrazine removal efficiency. Furthermore, the adsorbed toxic contaminants on the TM nanorobots can be disposed by a simple cooling process and exhibit good recovery retention after multiple reuse cycles. This combination of temperature sensitive aggregation/separation coupled with magnetic propulsion opens a plethora of opportunities in the applicability of nanorobots in water treatment and targeted pollutant removal approaches.

Silicane Derivative Increases Doxorubicin Efficacy in an Ovarian Carcinoma Mouse Model: Fighting Drug Resistance.

The development of cancer resistance continues to represent a bottleneck of cancer therapy. It is one of the leading factors preventing drugs to exhibit their full therapeutic potential. Consequently, it reduces the efficacy of anticancer therapy and causes the survival rate of therapy-resistant patients to be far from satisfactory. Here, an emerging strategy for overcoming drug resistance is proposed employing a novel two-dimensional (2D) nanomaterial polysiloxane (PSX). We have reported on the synthesis of PSX nanosheets (PSX NSs) and proved that they have favorable properties for biomedical applications. PSX NSs evinced unprecedented cytocompatibility up to the concentration of 300 µg/mL, while inducing very low level of red blood cell hemolysis and were found to be highly effective for anticancer drug binding. PSX NSs enhanced the efficacy of the anticancer drug doxorubicin (DOX) by around 27.8-43.4% on average and, interestingly, were found to be especially effective in the therapy of drug-resistant tumors, improving the effectiveness of up to 52%. Fluorescence microscopy revealed improved retention of DOX within the drug-resistant cells when bound on PSX NSs. DOX bound on the surface of PSX NSs, i.e., PSX@DOX, improved, in general, the DOX cytotoxicity in vitro. More importantly, PSX@DOX reduced the growth of DOX-resistant tumors in vivo with 3.5 times better average efficiency than the free drug. Altogether, this paper represents an introduction of a new 2D nanomaterial derived from silicane and pioneers its biomedical application. As advances in the field of material synthesis are rapidly progressing, novel 2D nanomaterials with improved properties are being synthesized and await thorough exploration. Our findings further provide a better understanding of the mechanisms involved in the cancer resistance and can promote the development of a precise cancer therapy.

Sulfonamido carboranes as highly selective inhibitors of cancer-specific carbonic anhydrase IX.

Carbonic anhydrase IX (CA IX) is a transmembrane enzyme overexpressed in hypoxic tumors, where it plays an important role in tumor progression. Specific CA IX inhibitors potentially could serve as anti-cancer drugs. We designed a series of sulfonamide inhibitors containing carborane clusters based on prior structural knowledge of carborane binding into the enzyme active site. Two types of carborane clusters, 12-vertex dicarba-closo-dodecaborane and 11-vertex 7,8-dicarba-nido-undecaborate (dicarbollide), were connected to a sulfonamide moiety via aliphatic linkers of varying lengths (1-4 carbon atoms; n = 1-4). In vitro testing of CA inhibitory potencies revealed that the optimal linker length for selective inhibition of CA IX was n = 3. A 1-sulfamidopropyl-1,2-dicarba-closo-dodecaborane (3) emerged as the strongest CA IX inhibitor from this series, with a Ki value of 0.5 nM and roughly 1230-fold selectivity towards CA IX over CA II. X-ray studies of 3 yielded structural insights into their binding modes within the CA IX active site. Compound 3 exhibited moderate cytotoxicity against cancer cell lines and primary cell lines in 2D cultures. Cytotoxicity towards multicellular spheroids was also observed. Moreover, 3 significantly lowered the amount of CA IX on the cell surface both in 2D cultures and spheroids and facilitated penetration of doxorubicin. Although 3 had only a moderate effect on tumor size in mice, we observed favorable ADME properties and pharmacokinetics in mice, and preferential presence in brain over serum.

Radioactive Uranium Preconcentration via Self-Propelled Autonomous Microrobots Based on Metal-Organic Frameworks.

Self-propelled micromachines have recently attracted attention for environmental remediation, yet their use for radioactive waste management has not been addressed. Engineered micromotors that are able to combine highly adsorptive capabilities together with fast autonomous motion in liquid media are promising tools for the removal of nuclear waste, which is one of the most difficult types to manage. Herein, we fabricate self-propelled micromotors based on metal-organic frameworks (MOFs) via template-based interfacial synthesis and show their potential for efficient removal of radioactive uranium. A crucial challenge of the MOF-based motors is their stability in the presence of fuel (hydrogen peroxide) and acidic media. We have ensured their structural stability by Fe doping of zeolitic imidazolate framework-8 (ZIF-8). The implementation of magnetic ferroferric oxide nanoparticles (Fe3O4 NPs) and catalytic platinum nanoparticles (Pt NPs) results in the magnetically responsive and bubble-propelled micromotors. In the presence of 5 wt % H2O2, these micromotors are propelled at a high speed of ca. 860 ± 230 µm·s-1 (i.e., >60 body lengths per second), which is significantly faster than that of other microrod-based motors in the literature. These micromotors demonstrate a highly efficient removal of uranium (96%) from aqueous solution within 1 h, with the subsequent recovery under magnetic control, as well as stable recycling ability and high selectivity. Such self-propelled magnetically recoverable micromotors could find a role in the management and remediation of radioactive waste.

Metallacarborane Sulfamides: Unconventional, Specific, and Highly Selective Inhibitors of Carbonic Anhydrase IX.

Carbonic anhydrase IX (CAIX) is a transmembrane enzyme that regulates pH in hypoxic tumors and promotes tumor cell survival. Its expression is associated with the occurrence of metastases and poor prognosis. Here, we present nine derivatives of the cobalt bis(dicarbollide)(1-) anion substituted at the boron or carbon sites by alkysulfamide group(s) as highly specific and selective inhibitors of CAIX. Interactions of these compounds with the active site of CAIX were explored on the atomic level using protein crystallography. Two selected derivatives display subnanomolar or picomolar inhibition constants and high selectivity for the tumor-specific CAIX over cytosolic isoform CAII. Both derivatives had a time-dependent effect on the growth of multicellular spheroids of HT-29 and HCT116 colorectal cancer cells, facilitated penetration and/or accumulation of doxorubicin into spheroids, and displayed low toxicity and showed promising pharmacokinetics and a significant inhibitory effect on tumor growth in syngenic breast 4T1 and colorectal HT-29 cancer xenotransplants.

Supercapacitors in Motion: Autonomous Microswimmers for Natural-Resource Recovery.

An electroadsorption technique similar to the ultrafast charging mechanism in supercapacitors is utilized to remove metals with different sizes and hydrophilicities from contaminated water using self-propelled microswimmers. The swimmers carry graphite fibre or bismuth with a layered crystal structure providing high electrostatic double-layer capacitances. Unlike previous methods, this electrochemical technique does not only utilize the surface of the swimmers, but due to the interlayer spacing of the graphite and bismuth, it is able to store metals in ≈400 layers, allowing removal and recovery of >50 ppm lithium in only 5 min. A larger interlayer distance between bismuth sheets allows the removal of bigger cations (sodium and calcium), expanding the application of this method to a large variety of natural elements. Finally, magnetic navigation of charged swimmers to an oxygen-saturated media causes oxidation and thus immediate release of the metal ions from the swimmers.

Germanane synthesis with simultaneous covalent functionalization: towards highly functionalized fluorescent germananes.

Monoelemental 2D-materials beyond graphene are attracting great attention. Although monolayer graphene or phosphorene can be prepared from its layered 3D form, graphite or black phosphorus, by exfoliation of a large van der Waals crystal, this route is not suitable for the preparation of 2D-germanene based materials due to the crystal structure and chemical properties of germanium. Unlike graphene or phosphorene, these materials are prepared by chemical exfoliation from bulk Zintl phases - here represented by calcium germanide. We describe the exfoliation and subsequent modification of calcium germanide, which yields layered germanium materials with alkyl or aryl groups. Different organic functional groups covalently attached to layered germanane exhibit a very intense fluorescence in the blue region, which makes them prospective materials for further application in optoelectronic devices. The described procedure for covalently functionalized germananes represents the way for the production of these materials.

Ultrapure Graphene Is a Poor Electrocatalyst: Definitive Proof of the Key Role of Metallic Impurities in Graphene-Based Electrocatalysis.

Graphene and its derivatives have been reported in many articles as "metal-free" carbon electrocatalytic materials. Its synthesis procedures are generally based on the chemical oxidation of graphite and subsequent thermal or chemical reduction. Because graphene oxide has a large surface area and typically contains a variety of oxygen functionalities, metallic ions (impurities) from reaction mixtures can be adsorbed on its surface. These impurities can significantly enhance the electrocatalytic activity and thus lead to data misinterpretation; such impure samples are referred to as "metal-free" catalysts. In this paper, we report the synthesis of impurity-free graphene, which is compared with graphene prepared by standard methods based on the thermal and chemical reduction of two graphene oxides. Detailed analysis of graphene prepared by standard methods shows a direct relation between metallic impurities and the electrocatalytic activity of graphene. In contrast, impurity-free graphene exhibits poor electrocatalytic activity.

Metal-Free Visible-Light Photoactivated C3N4 Bubble-Propelled Tubular Micromotors with Inherent Fluorescence and On/Off Capabilities.

Photoactivated micromachines are at the forefront of the micro- and nanomotors field, as light is the main power source of many biological systems. Currently, this rapidly developing field is based on metal-containing segments, typically TiO2 and precious metals. Herein, we present metal-free tubular micromotors solely based on graphitic carbon nitride, as highly scalable and low-cost micromachines that can be actuated by turning on/off the light source. These micromotors are able to move by a photocatalytic-induced bubble-propelled mechanism under visible light irradiation, without any metal-containing part or biochemical molecule on their structure. Furthermore, they exhibit interesting properties, such as a translucent tubular structure that allows the optical visualization of the O2 bubble formation and migration inside the microtubes, as well as inherent fluorescence and adsorptive capability. Such properties were exploited for the removal of a heavy metal from contaminated water with the concomitant optical monitoring of its adsorption by fluorescence quenching. This multifunctional approach contributes to the development of metal-free bubble-propelled tubular micromotors actuated under visible light irradiation for environmental applications.

One-Step Synthesis of B/N Co-doped Graphene as Highly Efficient Electrocatalyst for the Oxygen Reduction Reaction: Synergistic Effect of Impurities.

In the last decade, numerous studies of graphene doping by various metal and nonmetal elements have been done in order to obtain tailored properties, such as non-zero band gap, electrocatalytic activity, or controlled optical properties. From nonmetal elements, boron and nitrogen were the most studied dopants. Recently, it has been shown that in some cases the enhanced electrocatalytic activity of graphene and its derivatives can be attributed to metal impurities rather than to nonmetal elements. In this paper, we investigated the electrocatalytical properties of B/N co-doped graphene with respect to the content of metallic impurities introduced by the synthesis procedures. For this purpose, a permanganate (Hummers) and a chlorate (Hofmann) route were used for the preparation of the starting graphene oxides (GO). The GO used for the synthesis of B/N co-doped graphene had significantly difference compositions of oxygen functionalities as well as metallic impurities introduced by the different synthetic procedures. We performed a detailed structural and chemical analysis of the doped graphene samples to correlate their electrocatalytic activity with the concentration of incorporated boron and nitrogen as well as metallic impurities.

Paramagnetic 19F Relaxation Enhancement in Nickel(II) Complexes of N-Trifluoroethyl Cyclam Derivatives and Cell Labeling for 19F MRI.

1,8-Bis(2,2,2-trifluoroethyl)cyclam (te2f) derivatives with two coordinating pendant arms involving methylenecarboxylic acid (H2te2f2a), methylenephosphonic acid (H4te2f2p), (2-pyridyl)methyl (te2f2py), and 2-aminoethyl arms (te2f2ae) in 4,11-positions were prepared, and their nickel(II) complexes were investigated as possible 19F MR tracers. The solid-state structures of several synthetic intermediates, ligands, and all complexes were confirmed by X-ray diffraction analysis. The average Ni···F distances were determined to be about 5.2 Å. All complexes exhibit a trans-III cyclam conformation with pendant arms bound in the apical positions. Kinetic inertness of the complexes is increased in the ligand order te2f2ae ≪ te2f < te2f2py ≈ H4te2f2p ≪ H2te2f2a. The [Ni(te2f2a)] complex is the most kinetically inert Ni(II) complex reported so far. Paramagnetic divalent nickel caused a shortening of 19F NMR relaxation time down to the millisecond range. Solubility, stability, and cell toxicity were only satisfactory for the [Ni(te2f2p)]2- complex. This complex was visualized by 19F MRI utilizing an ultrashort echo time (UTE) imaging pulse sequence, which led to an increase in sensitivity gain. Mesenchymal stem cells were successfully loaded with the complex (up to 0.925/5.55 pg Ni/F per cell).19F MRI using a UTE pulse sequence provided images with a good signal-to-noise ratio within the measurement time, as short as tens of minutes. The data thus proved a major sensitivity gain in 19F MRI achieved by utilization of the paramagnetic (transition) metal complex as 19F MR tracers coupled with the optimal fast imaging protocol.

Graphane Nanostripes.

Graphane, the hydrogenated counterpart of graphene, was shown to exhibit properties such as tunable band gaps through varied degrees of hydrogenation, fluorescence, or ferromagnetism. Graphane nanostripe properties have also been theoretically predicted. Herein, we show that graphane nanostripes can be prepared by opening carbon nanotubes using Birch reduction in liquid ammonia utilizing potassium as a reducing agent and water as a proton donor. The prepared graphane nanostripes exhibit several exceptional properties when coupled with trace metal dopants. The interplay of metallic nanoparticles and defects lead to a spin polarization and induction of ferromagnetic moment, as well as to enhanced electrocatalytic properties in the hydrogen evolution reaction when compared to non-hydrogenated carbon nanotubes.

Partially Hydrogenated Graphene Materials Exhibit High Electrocatalytic Activities Related to Unintentional Doping with Metallic Impurities.

Partially hydrogenated graphene materials, synthesized by the chemical reduction/hydrogenation of two different graphene oxides using zinc powder in acidic environment or aluminum powder in alkaline environment, exhibit high electrocatalytic activities, as well as electrochemical sensing properties. The starting graphene oxides and the resultant hydrogenated graphenes were characterized in detail. Their electrocatalytic activity was examined in the oxygen reduction reaction, whereas sensing properties towards explosives were tested by using picric acid as a redox probe. Findings indicate that the high electrocatalytic performance originates not only from the hydrogenation of graphene, but also from unintentional contamination of graphene with manganese and other metals during synthesis. A careful evaluation of the obtained data and a detailed chemical analysis are necessary to identify the origin of this anomalous electrocatalytic activity.

Multifunctional electrocatalytic hybrid carbon nanocables with highly active edges on their walls.

Graphene sheets exhibit fast heterogeneous electron transfer at the edges while at the basal plane the electron transfer is much slower. Carbon nanotubes (CNTs) represent fascinating quasi-1-dimensional materials due to their electronic and mechanical properties which enable the formation of (unlike graphene) robust, flexible and well defined three dimensional structures. Because CNTs are created from "rolled up" graphene sheets, exposing mostly inactive walls, they generally exhibit poor electrochemical properties. In contrast, graphene sheets can exhibit fast electron transfer rates but are often prone to "restacking" which hinders their true electrochemical potential. Here we obviate this problem by partial unzipping of CNTs, where their inner core creates nanocables with high electrical conductivity while the outer unzipped graphene layers full of edges and defects act as highly electroactive materials. Metallic nanoparticles are introduced into graphene oxide/CNT hybrid structures (GOCNT), so they do catalyze reactions which are not catalyzed by carbon. We show that in combination with trace metal doping, these nanocables act as efficient electrocatalysts towards oxidation of biomarkers and energy related applications, such as hydrogen evolution reaction. Such hybrid graphene/CNT/metallic nanoparticles present universal well-structured catalysts which should find wide applications in electrochemical devices. GOCNTs rich in oxygenated groups show much promise in pollution management, thus their adsorption behaviour was investigated to establish their ability to remove harmful heavy-metal pollutants. The results show an increasing trend in the concentration of oxygen functional groups, directly correlated with the GOCNT adsorption capacity.

Synthetic routes contaminate graphene materials with a whole spectrum of unanticipated metallic elements.

The synthesis of graphene materials is typically carried out by oxidizing graphite to graphite oxide followed by a reduction process. Numerous methods exist for both the oxidation and reduction steps, which causes unpredictable contamination from metallic impurities into the final material. These impurities are known to have considerable impact on the properties of graphene materials. We synthesized several reduced graphene oxides from extremely pure graphite using several popular oxidation and reduction methods and tracked the concentrations of metallic impurities at each stage of synthesis. We show that different combinations of oxidation and reduction introduce varying types as well as amounts of metallic elements into the graphene materials, and their origin can be traced to impurities within the chemical reagents used during synthesis. These metallic impurities are able to alter the graphene materials' electrochemical properties significantly and have wide-reaching implications on the potential applications of graphene materials.

Searching for magnetism in hydrogenated graphene: using highly hydrogenated graphene prepared via Birch reduction of graphite oxides.

Fully hydrogenated graphene (graphane) and partially hydrogenated graphene materials are expected to possess various fundamentally different properties from graphene. We have prepared highly hydrogenated graphene containing 5% wt of hydrogen via Birch reduction of graphite oxide using elemental sodium in liquid NH3 as electron donor and methanol as proton donor in the reduction. We also investigate the influence of preparation method of graphite oxide, such as the Staudenmaier, Hofmann or Hummers methods on the hydrogenation rate. A control experiment involving NaNH2 instead of elemental Na was also performed. The materials were characterized in detail by electron microscopy, infrared spectroscopy, X-ray photoelectron spectroscopy, Raman spectroscopy both at room and low temperatures, X-ray fluorescence spectroscopy, inductively coupled plasma optical emission spectroscopy, combustible elemental analysis and electrical resistivity measurements. Magnetic measurements are provided of bulk quantities of highly hydrogenated graphene. In the whole temperature range up to room temperature, the hydrogenated graphene exhibits a weak ferromagnetism in addition to a contribution proportional to field that is caused not only by diamagnetism but also likely by an antiferromagnetic influence. The origin of the magnetism is also determined to arise from the hydrogenated graphene itself, and not as a result of any metallic impurities.